Menif S, Omri H, Hafsia R, Ben Romdhane N, Turki S, Meddeb B, Dellagi K
Laboratoire d'hématologie moléculaire et cellulaire, institut Pasteur de Tunis, Le-Belvedere, Tunis, Tunisie.
Pathol Biol (Paris). 2007 Jun;55(5):242-5. doi: 10.1016/j.patbio.2006.10.002. Epub 2006 Nov 29.
Hypereosinophilic syndromes (HES) are a heterogenous group of rare disorders characterized by sustained and otherwise unexplained overproduction of eosinophils with organ involvement and consecutive dysfunction. Detection of the FIP1L1-PDGFRA fusion gene or the corresponding cryptic 4q12 deletion in HES supports the diagnosis of chronic eosinophilic leukemia (CEL) and provides a molecular explanation for the pathogenesis of this disorder. We screened seven Tunisian patients fulfilling the WHO criteria of HES for the presence of the FIP1L1-PDGFRA fusion gene using nested reverse transcription polymerase chain reaction on peripheral blood samples. Four of the seven patients were positive for this fusion gene. Sequence analysis revealed a substantial heterogeneity of the fusion transcripts due to the involvement of several FIP1L1 exons. All patients were male. The median age at diagnosis was 24 years (range, 18-50); one patient had a history of hypereosinophilia of more than 10 years. Two patients had clinically important and symptomatic eosinophilic endomyocardial disease with thrombotic events. Splenomegaly was constant in FIP1L1-PDGFRA positive CEL but not in the other HES patients (only 1/3).
高嗜酸性粒细胞综合征(HES)是一组异质性罕见疾病,其特征为嗜酸性粒细胞持续且原因不明的过度生成,并伴有器官受累及随后的功能障碍。在HES中检测到FIP1L1-PDGFRA融合基因或相应的隐匿性4q12缺失支持慢性嗜酸性粒细胞白血病(CEL)的诊断,并为该疾病的发病机制提供了分子解释。我们使用巢式逆转录聚合酶链反应对外周血样本进行检测,筛查了7例符合WHO标准的突尼斯HES患者,以确定是否存在FIP1L1-PDGFRA融合基因。7例患者中有4例该融合基因呈阳性。序列分析显示,由于多个FIP1L1外显子的参与,融合转录本存在显著异质性。所有患者均为男性。诊断时的中位年龄为24岁(范围18 - 50岁);1例患者有超过10年的高嗜酸性粒细胞血症病史。2例患者患有具有临床重要性且有症状的嗜酸性粒细胞性心内膜疾病并伴有血栓形成事件。FIP1L1-PDGFRA阳性的CEL患者均有脾肿大,而其他HES患者中则无(仅1/3)。